Abstract
Avanafil (AV) is the phosphodiesterase (PDE) type 5 inhibitor drug used in erectile dysfunction, having pyrrolidine, pyrimidine, carboxamide, and chlorine as functional groups which can easily break by environmental changes and cause toxicity. Henceforth, in detail, HPLC stability study with the Quality-by-Design (QbD) approach is presented which leads to recommended storage conditions. The stability of AV was analyzed in hydrolysis, photolysis, and thermal and oxidative conditions. The application of the QbD approach during the stability method development comprises steps as screening and optimization. Quality target product profile (QTPP) was defined, and critical quality attributes (CQAs) were assigned to meet the QTPP requirements. Primary parameters obtained from the Ishikawa diagram were studied via Placket–Burman, and four critical factors were optimized through the central composite design (CCD). The finalized method includes mobile phase [10 mM ammonium acetate, pH 4.5 adjusted by acetic acid:ACN (60:40, v/v)] at 0.9-mL/min flow rate and 239-nm wavelength. A control strategy was set up to ensure that the method repeatedly meets the acceptance criteria. Overall, 16 degradation product peaks of AV in all conditions (solid and solution state) were identified with optimized method and evaluated by HPLC-PDA study. A comprehensive systemic optimization of AV stability study is stated for the first time, which reveals that AV is prone to degrade in sunlight, moisture, and temperature. Global regulators and manufacturers should take care of the packaging, handling, and labeling of AV. A fully validated LC–MS compatible stability method can be successfully applied to monitor AV stability from its formulation which can be wisely extrapolated to assess the AV from biological samples.Graphical abstract
Highlights
Stability testing is an important step in the drug approval process to assess a drug substance or drug product quality, which varies with time under the influence of environmental factors such as temperature, humidity, and light
Quality by Design instability method Identification of Quality target product profile (QTPP) and critical quality attributes (CQAs) It is considered as the first step in QbD-based stability method development
Nowadays, the term quality is highly focused by regulatory authorities; continuous monitoring of each parameter during every step becomes more crucial for pharmaceutical companies
Summary
Stability testing is an important step in the drug approval process to assess a drug substance or drug product quality, which varies with time under the influence of environmental factors such as temperature, humidity, and light. The common practice in the past was to develop a stability-indicating method using a trial and error approach called as one factor at a time (OFAT). The trials were taken to get resolved peaks until the best method was found. It was time-consuming and required a large number of experiments which often resulted in a nonrobust performance (Maggio et al 2013). The stabilityindicating method development using the Quality-byDesign (QbD) approach offers more accurate and robust results related to the OFAT approach, which comprises screening and optimization as steps (Schmidt and Molnár 2013; Tol et al 2016, 2020; Karmarkar et al 2011). Several reports focus on application of the QbD approach for analytical method development using design of experiment as one of the element (Hubert et al 2014; Gavin and Olsen 2008). An attempt was made to develop a robust stability-indicating method with the QbD approach for Avanafil (AV)
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